We are requesting R13 conference support for a new conference series addressing bradykinin-mediated angioedema. We have proposed three conferences that will in a sequential and increasingly ambitious manner push the research agenda and our understanding of bradykinin-mediated angioedema. The first conference will be held September 19-20, 2014 in San Diego and is entitled Defining boundaries of our HAE knowledge. This conference will include three scientific sessions. Session #1: What don't we know about bradykinin generation and action in angioedema? Talks will address: Regulation of BKR expression and signaling, possible insights into angioedema; Genetic and acquired mechanisms for the increased risk of BK-mediated angioedema in African-Americans and other populations; and Impact of sex hormones on the generation and degradation of bradykinin, and its relevance to angioedema. Session #2: New horizons in the diagnosis and treatment of BK-mediated AE. Talks will address: Serpinopathies and protein folding: Lessons from the alpha1-antitrypsin deficiency experience; and Developing assays of bradykinin generation for the diagnosis of bradykinin-mediated angioedema; and Treating a rare disease - how should we approach the pharmacoeconomics of HAE care? Session #3: Barriers to optimal diagnosis and treatment of HAE. Talks will address: Patient registries in rare diseases: Optimal designs and uses to improve patient outcomes; Special challenges in the diagnosis and treatment of children with HAE; and Special challenges in the diagnosis and treatment of angioedema in women. The second conference in 2016 will be entitled 2016: Deciphering determinants of disease severity in HAE, and will address: Transduction and modulation of stress in HAE; Genetics& epigenetics of HAE disease severity; and Pharmacogenomics: Picking the optimal treatment for a patient. The final conference in 2018 will be entitled Considering a cure for HAE and will address: Gene therapy; Gene correction; and Molecular chaperones. The central goal of this conference is to provide a highly interactive, interdisciplinary forum for scientific exchange and collaboration amongst junior and senior scientists who study angioedema. A second objective is to foster the development and interests of younger investigators to help support their careers and provide a new generation of angioedema investigators. The conference consists of plenary and poster sessions as well as smaller breakout sessions to stimulate discussion and get all participants involved. The plenary sessions will be topical and combine state of the art talks from leaders outside the angioedema field followed by talks from experts in the field. We expect that this cross-fertilization will help stimulate novel approaches to the study of angioedema. The timing of the meetings is fortuitous in that the development of novel therapeutic agents has stimulated significant interest in bradykinin-mediated angioedema; however, the pathophysiologic understanding and diagnostic techniques to address these diseases remains relatively poorly developed.